Dimethylformamide → 7-(1,4-Diazabicyclo[3.2.1]octan-4-yl)-6,8-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

HRID 1939275Notes

Reaction equation

HRID 1939275 reaction equation
CN(C)C=O.[F:6][C:7]1[C:8]([CH3:27])=[C:9]2[C:14](=[C:15]([F:18])[C:16]=1F)[N:13]([C@@H:19]1[CH2:21][C@@H:20]1[F:22])[CH:12]=[C:11]([C:23]([OH:25])=[O:24])[C:10]2=[O:26].Cl.Cl.[N:30]12[CH2:37][CH:34]([CH2:35][CH2:36]1)[NH:33][CH2:32][CH2:31]2>C(N(CC)CC)C>[N:30]12[CH2:37][CH:34]([CH2:35][CH2:36]1)[N:33]([C:16]1[C:15]([F:18])=[C:14]3[C:9]([C:10](=[O:26])[C:11]([C:23]([OH:25])=[O:24])=[CH:12][N:13]3[C@@H:19]3[CH2:21][C@@H:20]3[F:22])=[C:8]([CH3:27])[C:7]=1[F:6])[CH2:32][CH2:31]2

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 123740781,4-Diazabicyclo[3.2.1]octane dihydrochlorideHCID 228799641-[(1R,2S)-2-Fluorocyclopropyl]-6,7,8-trifluoro-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic Acid

Product 1

HCID 228799667-(1,4-Diazabicyclo[3.2.1]octan-4-yl)-6,8-difluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic AcidYield 62.3%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

To 5 ml of dried N,N-dimethylformamide were added 211 mg of 6,7,8-trifluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 372 mg of 1,4-diazabicyclo[3.2.1]octane dihydrochloride, and 2 ml of triethylamine, and the mixture was stirred at 100° C. for 1 hour. After allowing to cool, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a 1N sodium hydroxide aqueous solution while cooling with ice. After neutralizing with 1N hydrochloric acid, the mixture was extracted with chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resulting crude crystals were recrystallized from a mixed solvent of ethanol and 28% aqueous ammonia. The precipitated crystals were collected by filtration, washed with diethyl ether, and dried at 60° C. in vacuo overnight to yield 170 mg of the titled compound as a yellow powder.

Workup

  1. temperatureto cool
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in a 1N sodium hydroxide aqueous solution
  4. temperaturewhile cooling with ice
  5. extractionthe mixture was extracted with chloroform
  6. dry with materialthe extract was dried over anhydrous sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe resulting crude crystals were recrystallized from a mixed solvent of ethanol and 28% aqueous ammonia
  9. filtrationThe precipitated crystals were collected by filtration
  10. washwashed with diethyl ether
  11. customdried at 60° C. in vacuo overnight

Sources & evidence

ORD record
ord-bb02766707044c7ea1b8c73623a4ff8d
Source dataset
uspto-grants-1997_12
Patent number
US05696132

Reaction notes

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